Kaposi's sarcoma (KS) is a devastating malignancy prevalent among immunosuppressed individuals, including AIDS patients and patients who have undergone organ transplants. The global seroprevalence of KSHV is uneven. It is endemic in sub-Saharan Africa where 40-60% of HIV-infected individuals are co-infected with Kaposi's sarcoma-associated herpesvirus (KSHV), the etiological agent for KS. In the United States, where the seroprevalence of KSHV in the normal population is low, KSHV infection remains high in HIV-1 infected individuals and in other high-risk groups. Reported data indicates that more than 60% of HIV positive individuals in the United States are also infected with KSHV. Currently, very little is known about the protective immune response against KSHV and no vaccine against this oncogenic virus is available. The overall goal of the proposed study is to develop an effective vaccine against KSHV. The specific approaches necessary to accomplish the goal are: 1) characterization of the glycoprotein B (gB) and identification of its neutralizing epitopes;2) identification of KSHV mimotopes that can be recognized by neutralizing antibodies using random peptide phage display;and 3) assessing the potential of the identified gB epitopes and phage displayed mimotopes as vaccine candidates by their ability to induce a neutralizing immune response in mice. The proposed study is significant and unique because it combines a traditional approach with an innovative phage display and immunofocusing approach to identify potential viral proteins and epitopes that can generate neutralizing antibodies, which can then be developed into effective vaccines against KSHV. PUBLIC HEALTH RELEVANCE: Kaposi's sarcoma (KS) is a devastating malignancy prevalent among immunosuppressed individuals, including AIDS patients and patients who have undergone organ transplants. The proposed study will result in the development of an effective vaccine to guard against the Kaposi's sarcoma-associated herpesvirus (KSHV), the etiological agent of KS.